Despite the clinical relevance of back pain and intervertebral disc herniation, the lack of reliable models has strained their molecular understanding. We characterized the lumbar spinal phenotype of C57BL/6 and SM/J mice during aging. Interestingly, old SM/J lumbar discs evidenced accelerated degeneration, associated with high rates of disc herniation. SM/J AF's and degenerative human's AF transcriptomic profiles showed altered immune cell, inflammation, and p53 pathways. Old SM/J mice presented increased neuronal markers in herniated discs, thicker subchondral bone, and higher sensitization to pain. Dorsal root ganglia transcriptomic studies and spinal cord analysis exhibited increased pain and neuroinflammatory markers associated with altered extracellular matrix regulation. Immune system single-cell and tissue level analysis showed distinctive T-cell and B-cell modulation and negative correlation between mechanical allodynia and INF-α, IL-1β, IL2, and IL4, respectively. This study underscores the multisystemic network behind back pain and highlights the role of genetic background and the immune system in disc herniation disease. Acknowledgments: This study is supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) R01AR055655, R01AR064733, R01AR074813 to MVR

Introduction. Herniated disc tissue removed at surgery usually appears degenerated, and MRI often reveals degenerative changes in adjacent discs and vertebrae. This has fostered the belief that a disc must be degenerated before it can herniate, which has medicolegal significance. We hypothesise that degenerative changes in herniated disc tissues differ from those found in tissues that have degenerated in-situ, and are consistent with being consequences rather than causes of herniation. Methods. Surgically-removed discs were examined using histology, immunohistochemistry and confocal microscopy. 21 samples of herniated tissues were compared with age-matched tissues excised from 11 patients whose discs had reached a similar Pfirrman grade of degeneration but without herniating. Degenerative changes were assessed separately in three tissue types (where present): nucleus, inner annulus, and outer annulus. Mann-Whitney U tests were used to compare ‘herniated’ vs ‘in-situ’ tissues. Results. Herniated tissues showed significantly greater cellularity (annulus), greater proteoglycan loss (outer annulus), greater neovascularisation (annulus), greater innervation (annulus) as judged by PGP 9.5 staining, greater expression of matrix-degrading enzymes MMP1 and MMP3 (inner annulus), but less cell clustering (outer annulus). Some similar but non-significant differences were seen in nucleus tissues. Interpretation. Herniated tissues that escape the pressurised confines of the disc are free to swell, lose proteoglycans and come into contact with blood cells. These events could explain most of the differences between herniated tissues and those that degenerated ‘in situ’. Results support our hypothesis, and warn against assuming that degenerative changes always precede (or cause) disc herniation. No conflicts of interest. No funding obtained. This abstract has not been previously published in whole or in part; nor has it been presented previously at a national meeting

Summary Statement. Repetitive loading of degenerated human intervertebral discs in combined axial compression, flexion and axial rotation, typical of manual handling lifing activities, causes: an increase in intradiscal maximum shear strains, circumferential annular tears and nuclear seperation from the endplate. Introduction. Chronic low back pain (LBP) is a crippling condition that affects quality of life and is a significant burden to the health care system and the workforce. The mechanisms of LBP are poorly understood, however it is well known that loss of intervertebral disc (disc) height due to degeneration is a common cause of chronic low back and referred pain. Gross disc injury such as herniation can be caused by sudden overload or by damage accumulation via repetitive loading, which is a cause of acute LBP and an accelerant of disc degeneration. The aim of this study was to determine for the first time the relationship between combined repetitive compression, flexion and axial rotation motion of degenerated cadaver lumbar spine segments, and the progression of three-dimensional (3D) internal disc strains that may lead to disc herniation and macroscopic tissue damage. Patients & Methods. Seven degenerated human lumbar functional spinal units (FSUs) underwent pre-test MRI, had a grid of tantalum wires inserted into the mid-transverse plane of the disc and were subjected to 20,000 cycles of repetitive loading in combined compression (1.7 MPa), flexion (11–13°) and right axial rotation (2–3°) in a six degree of freedom hexapod robot. Stereoradiographs were taken at cyclic intervals (1, 500, 1000, 5000, 10000, 15000 and 20000 cycles) from which 3D intradiscal principal strains and maximum shear strains (MSS) were calculated and partitioned into nine disc anatomical regions. After testing the discs underwent post-test MRI followed by macroscopic assessment to identify tissue damage. A repeated measures ANOVA having a within-subjects factor of cycle number, and a between-subjects factor of disc region was used to examine the effects of cycle number and disc region on MSS. Results. No visible evidence of disc herniation occurred after 20,000 cycles, however circumferential annular tears and nucleus separation from the endplate were observed in all specimens in agreement with observed signal changes in post-test MRI images. There was a significant effect of both cycle number, disc region and the interaction of cycle number x disc region on MSS (p<0.001). MSS was significantly larger after 20,000 cycles compared with the first loading cycle in the anterior, left anterolateral, left lateral, and left posterolateral disc regions (p<0.037). Minor changes in MSS were seen in the posterior and nucleus regions. The largest increases were observed in the left anterolateral and left posterolateral regions after 20,000 cycles. Discussion/Conclusion. A significant increase in MSS was observed across most regions in the disc after 20,000 repetitive loading cycles, especially in the left anterolateral and left posterolateral regions. No herniation was observed, although macroscopic and MRI evidence of circumferential annular tears and nuclear separation from the endplate occurred, suggesting internal disc tissue disorganisation that may indicate a progression towards eventual herniation

Injury of the intervertebral disc (IVD) can occur for many reasons including structural weakness due to disc degeneration. A common disc injury is herniation. A herniated nucleus can compress spinal nerves, causing pain, and nucleus depressurisation changes mechanical behaviour. Many studies have investigated in vitro IVD injuries including endplate fracture, incisions, and nucleotomy. There is, however, a lack of consensus on how the biomechanical behaviour of spinal motion segments is affected. The aim of this study was to induce defined changes to IVDs of spine specimens in vitro and apply 6 degree of freedom testing to evaluate the effect of these changes. Six porcine lumbar spinal motion segments were harvested from organically farmed pigs. Posterior structures were removed to produce isolated spinal disc specimens. Specimens were potted in Wood's metal, ensuring the midplane of the IVD remained horizontal. After potting, specimens were sprayed with 0.9% saline, wrapped in saline-soaked tissue and plastic wrap to prevent dehydration. A 400N axial preload was equilibrated for 30 minutes before testing. Specimens were tested intact and after a partial nucleotomy removing ~0.34g of nuclear material with a curette through an annular incision. Stiffness tests were performed using the University of Bath's custom 6-axis spine simulator with coordinate axes and displacement amplitudes. Tests comprised five cycles with data acquired at 100Hz. Stiffness matrices were evaluated from the last three motion cycles using the linear least squares method. Stiffness matrices for intact and nucleotomy tests were compared. No significant differences in shear, axial or torsional stiffnesses were noted. Nucleotomy caused significantly higher stiffness in lateral bending and flexion-extension with increased linearity and the load-displacement behaviour in these axes displayed no neutral zone (NZ). Induced changes were designed to replicate posterolaterally herniated discs. Unaffected shear, axial and torsional stiffnesses suggest the annulus is crucial in these axes. However, reduced ROM and NZ after nucleotomy suggests bending is most affected by herniation. Increased linearity and lack of defined NZ in these axes demonstrates herniation causes major changes to the viscoelastic behaviour of spine specimens in response to loading

Abstract. Objectives. There is still controversy in the literature over whether Cervical Foraminotomy or Anterior Cervical discectomy and fusion (ACDF) is best for treating cervical Radiculopathy. Numerous studies have focused on the respective complication rates of these procedures and outcome measures with a lack of due consideration to preoperative MRI findings. Proximal foraminal stenosis can theoretically be accessed via either approach. We aimed to investigate whether patient reported outcome measures (PROMs) favoured one approach over the other in patients with proximal foraminal stenosis. Methods. A single centre retrospective review of patients undergoing either ACDF or Cervical foraminotomy over the period 2012 to 2022. VAS, Neck disability index (NDI), EQ5DL and Patient Satisfaction on a Five Point Likert scale were obtained. Patients who had both an ACDF and a Foraminotomy were excluded. Axial MRI images were analysed and the location of the worst clinically relevant disc herniation stratified as follows: Central (1), Paracentral (2) and Foraminal (3). Correlations and average PROMs were analysed in SPSS. Results. PROMs scores were available for 33 ACDF patients and 37 Foraminotomy patients. Average surgery time in ACDF group was 167 minutes while Foraminotomy 142 minutes. Average Length of hospital stay was 6.24 days in the Foraminotomy group and 3.54 days in the ACDF group. 18 patients were excluded due to having both surgeries (2 of which developed CSF leaks postoperatively). Of the included patients there were no postoperative complications. 13 patients in the ACDF had Central or Paracentral stenosis in addition to proximal Foraminal stenosis, 3 patients in the Foraminotomy group had some significant Paracentral herniation just before the Proximal foramen. The majority of patients in both groups had pure proximal Foraminal stenosis (N= 17 (ACDF), 20 (Foraminotomy). The results showed no significant difference in PROMs between patients who received an ACDF or a Foraminotomy for Proximal foraminal stenosis (EQ5DL, NDI, and satisfaction, P= 0.268, 0.253 and 0.327). There was no correlation between location of the stenosis and PROM scores in either group. Conclusions. Our data suggest that Proximal foraminal stenosis can be effectively addressed by either an anterior ACDF or a Foraminotomy with no difference in complication rates. Foraminotomy has the benefit of no implant cost but longer hospital stay. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Introduction. Risk factors for disc degeneration depend on how the condition is defined, i.e. on the specific disc degeneration “phenotype”. We present evidence that there are two major and largely-distinct types of disc degeneration. Methods. The relevant research literature was reviewed and re-interpreted. Evidence. In the . upper. lumbar and thoracic spine, disc degeneration is closely associated with endplate defects and with inflammatory changes in the vertebral bodies. It has a relatively high heritability (i.e. a strong genetic influence), and its incidence does not increase markedly with age. In the . lower. lumbar spine, disc degeneration is closely associated with radial fissures and nucleus herniation. Here it has a relatively low heritability, and a correspondingly stronger association with mechanical loading, and its incidence increases steadily throughout life. Mechanical experiments on cadaveric spines show that endplate fracture and nucleus herniation can be caused by compressive loading, and by bending combined with compression, respectively. Both lesions cause an immediate decompression of the nucleus, so that it becomes difficult to create subsequently the other lesion in the same disc. This suggests distinct phenotypes. Interpretation. The two types of disc degeneration are not entirely distinct, because disc herniation sometimes occurs at upper lumbar levels. Nevertheless, it may be useful to recognise two phenotypes when it comes to explaining and treating discogenic pain. Some other common disc changes (such as water loss and bulging) are attributable to ageing rather than degeneration, whereas disc narrowing probably represents a final common pathway for both types of disc degeneration. Conflicts of Interest. None. Source of Funding. None. This abstract has not been previously published in whole or in part; nor has it been presented previously at a national meeting

A suitable wound closure is an indispensable requirement for an uncomplicated and expedient recovery after an abdominal surgery. The closure technique will have a great impact on the healing process of the wound. Surgical complications, such as wound dehiscence (sometimes associated with evisceration), infection, hernia, nerve injury and incisional pain are very common in the postoperative period of an abdominal surgery. Besides, although their development can be promoted by other risk factors like age, sex, lifestyle, diet, health condition, the closure method can also influence the emergence of these undesirable complications. For this reason, and having the wellbeing and quality of life of the patients in mind, particularly high-risk patients, a closure system consisting of anchors applied on either side of the wound that aims to reduce the tension caused on the surrounding tissues of a wound and, consequently, decrease the risk of herniation was evaluated in a pilot animal study and compared with the traditional suture approach

Extensive annulus fibrosus (AF) radial tears lead to intervertebral disc (IVD) herniation. While unrepaired defects in the AF are associated with postoperative reherniation and high IVD degeneration prevalence, current surgical strategies are limited to symptomatic treatment of pain and disregard the structural integrity of the AF. For all these reasons, this study is focused on i) designing polycaprolactone (PCL) electrospun implants that mimic the multi-lamellar fibrous structure of the native tissue and ii) assessing their ability to properly close and repair an AF defect in a sheep in vivo model. Oriented PCL mats were produced by electrospinning with average fiber diameters of 1.3µm and a tensile modulus (55±1MPa) matching the one of a native human AF lamella (∼47MPa). In vitro experiments demonstrated a spontaneous colonization of PCL mats by human and ovine AF cells. In vivo study was carried out on 6 sheep in which 5 lumbar discs were exposed using a left retroperitoneal approach. Defects (2×5mm, 2mm depth) were created in the outer annulus, with randomized distribution of conditions including 10-layer oriented or non-oriented mats, untreated and healthy groups. X-ray and MRI examinations were performed every month until explantations at 1, 3 and 6 months, followed by immuno-histological analysis. Data showed no dislocation of the implants, cell infiltration between the PCL mats and within the mats, and a continuous type I collagen tissue formation between the implants and the surrounding AF tissue. These results highlight that multi-layer PCL electrospun mat is a promising biomaterial for AF repair

Background. Proteoglycans (PGs) have long been known to be important to the functioning of the intervertebral disc. The most common PG is aggrecan, but there are also small leucine-rich proteoglycans (SLRPs) which constitute only a small percentage of the total PGs. However, they have many important functions, including organising the collagen, protecting it from degradation and attracting growth factors to the disc. We have examined how the core proteins of these molecules vary in intervertebral discs from patients with different pathologies. Methods. Discs were obtained from patients with scoliosis (n=7, 19–53y), degenerative disc disease (DDD) (n=6, 35–51y) and herniations (n=5, 33–58y). Proteoglycans were extracted and the SLRPs (biglycan, decorin, fibromodulin, keratocan and lumican) were characterised via Western blotting following enzymatic digestion with chondroitinase ABC and keratanase. Results. At least some SLRPs were present in all the discs studied. In addition to the presence of intact SLRP core proteins there was evidence of fragmentation of all the core proteins but especially of biglycan, fibromodulin and keratocan. Biglycan and keratocan were present in the majority of samples with biglycan being highly fragmented in the majority and keratocan usually present as 2 molecular weight bands. Fibromodulin was present in all samples except for 1 scoliotic disc and usually showed a high degree of fragmentation. The intact core protein of lumican was detected in all samples and was only present as a fragment in one of the older scoliosis samples. Decorin was present in a few samples of which half showed fragmentation. Conclusion. Although the number of samples investigated so far is low, fragmentation of these SLRP molecules appears common in the pathological intervertebral disc. These findings are useful not only in helping unravel pathways of disc degeneration, but may also provide early biomarkers of the different pathologies. Conflicts of Interest. None. Source of Funding. None. Acknowledgements: MRC and AR UK for financial support of SR & SO

Objectives

Degenerative disc disease (DDD) and osteoarthritis (OA) are relatively frequent causes of disability amongst the elderly; they constitute serious socioeconomic costs and significantly impair quality of life. Previous studies to date have found that aggrecan variable number of tandem repeats (VNTR) contributes both to DDD and OA. However, current data are not consistent across studies. The purpose of this study was to evaluate systematically the relationship between aggrecan VNTR, and DDD and/or OA.

Human bone-marrow mesenchymal stem cells have an important role in the repair of musculoskeletal tissues by migrating from the bone marrow into the injured site and undergoing differentiation. We investigated the use of autologous human serum as a substitute for fetal bovine serum in the ex vivo expansion medium to avoid the transmission of dangerous transfectants during clinical reconstruction procedures.

Autologous human serum was as effective in stimulating growth of bone-marrow stem cells as fetal bovine serum. Furthermore, medium supplemented with autologous human serum was more effective in promoting motility than medium with fetal bovine serum in all cases. Addition of B-fibroblast growth factor to medium with human serum stimulated growth, but not motility. Our results suggest that autologous human serum may provide sufficient ex vivo expansion of human bone-marrow mesenchymal stem cells possessing multidifferentiation potential and may be better than fetal bovine serum in preserving high motility.